When theory and reality clash: When is the best time to try minocycline for Rheumatoid Arthritis?

Rheumatoid arthritis (RA) patients, initially elated, relieved, and hopeful to discover that minocycline is an approved, relatively safe and effective disease-modifying anti-rheumatic drug (DMARD), report frequently that they are subsequently left feeling confused and upset that their doctor has been unwilling to prescribe it. The following article outlines an apparent clash of expert-recommended theory and prescribing-reality and how this dynamic may have contributed to the sidelining of minocycline.


When Theory and Reality Clash: When is the best time to try minocycline for Rheumatoid Arthritis?

On May 30th, 2008, the American College of Rheumatology (ACR) published their “… recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis.” In this report, rheumatology experts recommended the use of “minocycline monotherapy” as a disease-modifying anti-rheumatic drug (DMARD) for use in patients with early, mild rheumatoid arthritis (RA), citing successful clinical studies to validate this recommendation. Of note, but not mentioned in this report, is that minocycline may also be combined safely with other DMARDs or biologic drugs.

“Clearly minocycline can provide adjunctive therapy for RA. In other words, minocycline can be combined with any other available agent. There are no exceptions! Examples include Plaquenil, methotrexate, Arava, anti-TNF compounds like Enbrel & Humira and the new intravenous drug, abetacept (Orencia). Decreased doses of one or both agents may help to avoid gastrointestinal side effects. This regimen usually reflects a desire to obtain additional improvement or to gradually convert to the safer drug, minocycline.”

Antibiotic Therapy for Rheumatic Disease: You know where we have been; so where are we now? David E. Trentham, M.D.

Since publication of the 2008 ACR treatment guidelines for RA, this recommendation has provided much encouragement to those who seek treatment with minocycline for RA, enabling patients to feel confident in asking their rheumatologist to support this treatment choice. However, the reality has been that many rheumatologists still decline to use minocycline as a DMARD, advising RA patients that there are “newer and better” drugs in use today. One of the confusing ironies of this reasoning, however, is that methotrexate (originally formulated to treat various cancers, such as breast and lung cancer, leukemia, osteosarcoma, and lymphoma) is still considered to be the “gold standard,” first-line DMARD for RA, even though this chemotherapeutic agent was first used off-label to treat RA in 1951. Minocycline, on the other hand, first arrived on the market 2 decades after methotrexate was first used to treat RA. A second-generation tetracycline, minocycline was originally synthesized by Lederle Laboratories in 1967, approved by the FDA in 1971, and was then sold under the brand name, Minocin, the following year.

Lending further confusion to this picture, three years after the ACR published their 2008 guidelines, a group of physician-researchers at the University of Nebraska published a retrospective study of minocycline and its use in clinical practice, finding that this DMARD option was not being offered in early, mild cases of RA as had been recommended. On the contrary, these authors concluded that,

“Rheumatologists have not embraced minocycline or doxycycline as primary treatment options for RA and reserve their use primarily in patients with long-standing, refractory disease.”

—Christopher J Smith, Harlan Sayles, Ted R Mikuls and Kaleb Michaud, University of Nebraska; Arthritis Research & Therapy;201113:R168

Due to the apparent clash between the ACR’s recommendations for optimal use of minocycline in RA and clinical reality, patients are confused and rightly so! Although recommended for use in early, mild disease, without poor prognosis, minocycline has been relegated to a last-resort DMARD to treat patients with long-standing RA where nothing else has worked. This, in spite of numerous studies and expansive patient experience demonstrating successful outcomes for all stages and degrees of severity of this debilitating disease. It is particularly perplexing why minocycline has been positioned as a low-priority RA medication when it has an exceptional safety profile; safe enough to be routinely prescribed for teen acne. Furthermore, if it’s effective enough to try in patients with long-standing, treatment-refractory RA, it should be equally, if not more effective for use in the newly diagnosed.

Dr. Thomas McPherson Brown, a practicing rheumatologist and researcher over the course of 5 decades, found that when minocycline was properly titrated to individual patient tolerance, and that all infectious co-factors were identified and appropriately treated, minocycline worked for patients with either early, mild RA or long-standing, severe RA. In fact, as described in The New Arthritis Breakthrough, authored by medical writer Henry Scammell, numerous rheumatic patients came to Dr. Brown’s clinic who were quite unwell, having suffered for years with poor results on other medications. This is not to say that minocycline is a “miracle cure,” producing swift results for all cases of RA. Response times vary, with some patients turning a corner very quickly and others who may need a good deal of patience to experience results. Scammell quotes Dr. Brown on his clinical observations in the book, as follows:

“In the most entrenched and recalcitrant cases, it can take up to thirty months from the beginning of therapy until the patient clearly turns the corner toward improvement, and the achievement of lasting remission can take several years… In shorter-term cases – and short term doesn’t necessarily mean less severe – complete remission can be achieved in less than six months.”

The New Arthritis Breakthrough, pages 269-270.

When talking with your rheumatologist about trying minocycline for your RA or that of a loved one, it might help to share a printed copy of the 2011 University of Nebraska study, which was conducted specifically for the purpose of determining the actual rheumatologist-prescribing patterns for the use of minocycline or doxycycline in RA. What this study revealed is evidence of a clash between ACR-recommendation theory versus prescribing-pattern reality!

Patient experience described to this foundation is that minocycline is a safe, effective DMARD option. By getting educated in advance about all the treatment options for RA and the possible serious side-effects that may be encountered, as well as having read through all the FAQs, Resources, and Research on this site, it should help to provide you with the confidence to discuss your preference to try minocycline in a well-informed manner with your treating physician.